Day 3 Durban: the revolution in ART arrives

The Treatment Evolution: New Drugs, New Reality session on Thursday afternoon was the most important session so far at the conference from the point of view of therapeutics.  Of great interest was the 48 week data for injectable cabotegravir + rilpivirine.

At this session the 48 week results for the ‘Cabotegravir + rilpivirine as long-acting maintenance therapy: LATTE‑2 week 48 results’ were presented by David Margolis (THAB0206LB).    This phase 2b study compared 4 week and 8 week injections vs oral therapy (CAB + ABC/3TC) to maintain viral suppression of HIV-1.

 309 patients ART-naïve HIV infected adults were treated during the 20 week induction period to reach a RNA< 50 c/mL with daily oral CAB 30 mg + ABC/3TC then were  randomized 2:2:1 to IM CAB LA + RPV LA every 4 weeks (Q4W), every 8 weeks (Q8W), or oral CAB + ABC/3TC (PO) in the Maintenance Period (MP).

 Key findings from this study were 

-          At Week 48, 92% (Q8W), 91% (Q4W), and 89% (PO) remained suppressed (ITT).  

-          More patients on Q8W (5%) than Q4W (< 1%) and PO (0%) had HIV-1 RNA >50 c/mL at Week 48. 

-          There were more discontinuations in Q8W (8%) and PO (9%) arms versus Q4W arm (1%).   

-          Injection sited reactions were common but resulted in < 1% withdrawal.  

-          Three subjects met criteria for viral failure during maintenance, one Q8W subject with emergent RPV and CAB resistance

 Q4W dosing resulted in lower rates of virologic non-response than Q8W so was selected for progression into phase 3 studies.  This treatment appears to be very effective and safe.   Questions remain about the acceptability of monthly injections in various clinical settings but this is a potentially the beginning of a whole new approach to HIV therapy.

Catherine Orrell  presented ‘Superior efficacy of dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) fixed dose combination (FDC) compared with ritonavir (RTV) boosted atazanavir (ATV) plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in treatment-naïve women with HIV-1 infection (ARIA Study)’.   (THAB0205LB) DTG/ABC/3TC was superior to ATV+RTV+FTC/TDF, with 82% and 71%, respectively, achieving HIV-1 RNA < 50 c/mL at Week 48.

Differences were driven by lower rates of both discontinuations due to adverse events (AEs) and virologic failures in the DTG/ABC/3TC group.  Of six DTG/ABC/3TC subjects who met protocol-defined virologic withdrawal criteria, none had resistance mutations, compared with 4 ATV+RTV+TDF/FTC subjects who met virologic withdrawal criteria of which one had an NRTI mutation, M184M/I/V. This study was very important in that it showed superiority and was female only.

Jean-Michel Molina  presented ‘Who benefited most from immediate treatment in START? A subgroup analysis’ (THAB0201).  In asymptomatic ART-naïve adults with >500 CD4 cells/mm³, immediate ART was superior to deferral across all subgroups.  People > 50, higher plasma HIV RNA level, lower baseline CD4 count, and higher Framingham risk had the greatest benefit.

Alejandro Arenas-Pinto presented ‘Increased risk of suicidal behaviour with use of efavirenz: results from the START trial’ (THAB0202). These findings suggest that participants using EFV in the immediate ART group had an increased risk of suicidal behaviour compared to ART-naïve controls. A prior psychiatric diagnosis increased the risk.

Michael Aboud  presented ‘STRIIVING: switching to abacavir/dolutegravir/lamivudine fixed dose combination (ABC/DTG/3TC FDC) from a PI, INI or NNRTI based regimen maintains HIV suppression at week 48’ (THAB0203).  Treatment experienced patients were randomized to continue current ART on Day 1 or switched to ABC/DTG/3TC.  The current treatment arm then switched at week 24.   In this switch arm 92% maintained viral suppression at 48 weeks (note the 24 week data has previously been presented).